HiFi long-read genomes for difficult-to-detect, clinically relevant variants.

Clinical short-read exome and genome sequencing approaches have positively impacted diagnostic testing for rare diseases. Yet, technical limitations associated with short reads challenge their use for the detection of disease-associated variation in complex regions of the genome. Long-read sequencing (LRS) technologies may overcome these challenges, potentially qualifying as a first-tier test for all rare diseases.

Exome variant prioritization in a large cohort of hearing-impaired individuals indicates IKZF2 to be associated with non-syndromic hearing loss and guides future research of unsolved cases.

Although more than 140 genes have been associated with non-syndromic hereditary hearing loss (HL), at least half of the cases remain unexplained in medical genetic testing. One reason is that pathogenic variants are located in 'novel' deafness genes. A variant prioritization approach was used to identify novel (candidate) genes for HL.

Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis.

While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated in silico IEI gene panel. Variants were classified and curated through expert review.

Long-Term Outcomes of Cochlear Implantation in Usher Syndrome.

Objectives: Usher syndrome (USH), characterized by bilateral sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP), prompts increased reliance on hearing due to progressive visual deterioration. It can be categorized into three subtypes: USH type 1 (USH1), characterized by severe to profound congenital SNHL, childhood-onset RP, and vestibular areflexia; USH type 2 (USH2), presenting with moderate to severe progressive SNHL and RP onset in the second decade, with or without vestibular dysfunction; and USH type 3 (USH3), featuring variable progressive SNHL beginning in childhood, variable RP onset, and diverse vestibular function. Previous studies evaluating cochlear implant (CI) outcomes in individuals with USH used varying or short follow-up durations, while others did not evaluate outcomes for each subtype separately.